UCLA Study Shows Early Brain Function Decline In Individuals With Alzheimer's Disease Gene

The study, appearing this week in the Proceedings of the National Academy of Sciences, combined genetic testing with positron emission tomography (PET) scanning to determine brain function in people at risk for Alzheimer's disease who still had normal memory function.

"This method may provide an effective way to detect Alzheimer's disease preclinically and test preventive therapies before permanent brain damage becomes extensive," said Dr. Gary Small, lead investigator and the Parlow-Solomon Professor on Aging and professor of psychiatry and biobehavioral sciences at UCLA.

UCLA researchers performed genetic testing on 54 adults, aged 50-84, with very mild and common age-related memory complaints. Half of the participants carried the apolipoprotein E-4 allele or APOE-4, a gene associated with Alzheimer's disease.

Each study participant received PET scans, a relatively new technology developed at UCLA. PET scans measure brain activity by revealing the amount of glucose metabolized throughout the brain. Unlike other brain imaging techniques, PET scans can differentiate Alzheimer's disease from the normal effects of aging.

Initial PET scans revealed that the group carrying the Alzheimer's gene had significantly lower function in the parietal and temporal regions of the brain, compared with the group without the APOE-4 gene. The temporal region is located at the temples and the parietal region is located above and behind the temples.

UCLA researchers conducted a two-year follow-up on 20 study participants. The group carrying the APOE-4 gene demonstrated a 5 percent function decline in these same two regions of the brain compared with their initial PET scans.

The group without the Alzheimer's gene demonstrated decline only in the frontal cortex, located in the front of the brain, which is consistent with normal aging. Results of memory testing, when researchers ask questions to measure forgetfulness and changes in memory, appeared normal for both groups at the beginning of the study and at the two-year follow-up.

"These findings indicate that brain function decline may begin to occur in the brain in individuals with APOE-4 long before the actual physical symptoms of Alzheimer's disease appear," said Small. "We found that a single copy of the APOE-4 gene was associated with lowered brain function in people with normal memory performance."

According to Small, the UCLA study is the first to report long-term PET results for individuals with the genetic risk for Alzheimer's who have no disease symptoms.

"We are now in a position to use these genetic and brain imaging tools to determine if we can prevent age-related memory decline and delay the onset of Alzheimer's disease," said Small.

"The UCLA study provides an important step in offering hope that we will eventually have an impact on Alzheimer's disease through prevention," said Dr. Barry Lebowitz, chief of the Adult/Geriatric Treatment and Prevention Research at the National Institute of Mental Health.

The UCLA research team has just announced a new UCLA Memory Clinic for testing treatments to prevent age-related memory loss. Studies will continue research into exploring the use of PET scanning and genetic testing.

The UCLA study was a collaborative effort between the UCLA Neuropsychiatric Institute, the UCLA Department of Molecular and Medical Pharmacology, the UCLA Brain Mapping Center, the UCLA Center on Aging, the UCLA Alzheimer's Disease Center, and the Center for Human Genetics at Duke University Medical Center.

Alzheimer's disease afflicts nearly 10 percent of people over age 65. The disease often begins with mild memory complaints and gradually progresses to dementia, which is a deterioration of most mental abilities including memory, language and higher intellectual functions. Victims eventually become bedridden, requiring total care.

The United States annually spends approximately $100 billion on Alzheimer's. Experts estimate that delaying the disease onset by five years could save $50 billion and reduce the expected number of cases by a million during the next decade.

The UCLA study was supported by grants from the National Institute on Mental Health, the National Institute of Aging, the Alzheimer's Association, the California Department of Health Services, the Department of Energy, the Sidell-Kagen Foundation, the Montgomery Street Foundation, the Fran and Ray Stark Foundation Fund for Alzheimer's Disease Research, the Brain Mapping Medical Research Organization, the Ahmanson Foundation, and the Tamkin Foundation.